Kuldyushev Nikita A, Mineev Konstantin S, Berkut Antonina A, Peigneur Steve, Arseniev Alexander S, Tytgat Jan, Grishin Eugene V, Vassilevski Alexander A
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
Moscow Institute of Physics and Technology (State University), Moscow, Russia.
Proteins. 2018 Oct;86(10):1117-1122. doi: 10.1002/prot.25583. Epub 2018 Sep 8.
Sodium channel alpha-toxins from scorpion venom (α-NaTx) inhibit the inactivation of voltage-gated sodium channels. We used solution NMR to investigate the structure of BeM9 toxin from Mesobuthus eupeus scorpion, a prototype α-NaTx classified as an "α-like" toxin due to its wide spectrum of activity on insect and mammalian channels. We identified a new motif that we named "arginine hand," whereby arginine side chain forms several hydrogen bonds with main chain atoms. The arginine hand was found in the "specificity module," a part of the molecule that dictates toxin selectivity; and just single arginine-to-lysine point mutation drastically changed BeM9 selectivity profile.
来自蝎毒的钠通道α-毒素（α-NaTx）可抑制电压门控钠通道的失活。我们利用溶液核磁共振技术研究了东亚钳蝎（Mesobuthus eupeus）的BeM9毒素的结构，BeM9毒素是一种典型的α-NaTx，因其对昆虫和哺乳动物通道具有广泛的活性而被归类为“α样”毒素。我们鉴定出了一个新的基序，将其命名为“精氨酸之手”，即精氨酸侧链与主链原子形成多个氢键。在“特异性模块”中发现了精氨酸之手，该模块是分子中决定毒素选择性的部分；仅仅一个精氨酸到赖氨酸的单点突变就极大地改变了BeM9的选择性谱。
